MORF-057

MORF-057 is a selective, oral small molecule inhibitor of the α4β7 integrin in development to treat patients suffering from inflammatory bowel disease (IBD) that is currently in phase 2b studies.

α4β7 has been validated as a target for the treatment of IBD by the success of the approved injectable (infused) antibody therapeutic vedolizumab. MORF-057, like vedolizumab, is designed to block the interactions between α4β7 on the surface of predominantly T-cells circulating in the bloodstream and the mucosal vascular addressin cell adhesion molecule 1, MAdCAM-1, substantially reducing lymphocyte migration from the bloodstream into intestinal mucosal tissues and avoiding inflammation that is associated with IBD. Our initial focus is on ulcerative colitis, one of the most common forms of IBD, with plans to investigate MORF-057 in Crohn’s disease with potential other gastrointestinal diseases to follow.
Clinical Trials

Morphic’s Phase 2 EMERALD program evaluates MORF-057 in patients with moderate-to-severe ulcerative colitis (UC)

The EMERALD-1 Phase 2a study achieved its primary endpoint, demonstrated consistent, clinically meaningful improvements across secondary and exploratory measures, and was well tolerated with no safety signal observed

In the EMERALD-1 open label Phase 2a study, MORF-057 demonstrated a statistically significant reduction of 6.4 points (p=0.002) from baseline at week 12 in the Robarts Histopathology Index (RHI) score and achieved 26% clinical remission as measured by Modified Mayo Clinic Score (mMCS).​

The EMERALD-2 global Phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 in patients with moderate-to-severe UC initiated in November 2022 and is enrolling as projected. Results are expected in the first half of 2025.

Phase 1 clinical studies of MORF-057 demonstrated a favorable safety and pharmacokinetic profile

In Phase 1 studies, α4β7 receptor occupancy greater than 99% was observed in multiple dose cohorts, exceeding pre-specified targets. Further, a series of preclinical results strongly support MORF-057 as a potential oral approach to α4β7 inhibition with results demonstrating similar activity and mechanistic patterns to vedolizumab.

For more information on the EMERALD clinical trials please click here.

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Integrin Partnership: Janssen

Morphic entered a research partnership with Janssen in 2019 to discover inhibitors of undisclosed integrin targets. In 2021, this partnership was expanded to include an antibody activator of an integrin target, extending the application of Morphic’s knowledge of integrin biology into modalities beyond small molecules. The antibody activator program is the focus of our collaboration with Janssen today.

Undisclosed Targets

Morphic is leveraging the MInT Platform to discover therapeutically relevant small molecule inhibitors of targets across the integrin family to treat autoimmune diseases, cancer and fibrotic diseases.

Undisclosed Target for Pulmonary Arterial Hypertension

Morphic is deploying the MInT Platform to create small molecule inhibitors of an undisclosed integrin target for evaluation as a potential treatment for pulmonary arterial hypertension (PAH). PAH is a devastating, usually fatal disease characterized by elevated mean pressures in the pulmonary artery and associated with lung and heart dysfunction. Morphic’s PAH program is in preclinical development.

αvβ8

Morphic is developing small molecule inhibitors of the integrin αvβ8 through a combination immuno-oncology approach for the treatment of solid tumors as well as potential additional indications. αvβ8 is known to activate selective isoforms of TGF-β and Morphic has demonstrated that αvβ8 inhibition can potentiate immune checkpoint blockade and potentially drive responses in checkpoint refractory tumors. Morphic’s αvβ8 inhibitors are in preclinical development.

Next Gen α4β7 Inhibitors

Morphic is developing a family of next generation α4β7 small molecule inhibitors with enhanced attributes using the MInT Platform. These candidates have distinct chemical properties from our first-generation inhibitors with differentiated selectivity, potency, and pharmacokinetic profiles. Morphic’s next generation α4β7 inhibitors are currently in preclinical development.